Effect of Perinatal Nicotine Exposure on the Development of Autonomic Responses

描述（由申请人提供）：候选人需要在发育神经生物学方面的额外知识技能，以使她能够继续阐明影响婴儿健康和福祉的因素的长期目标，并开发适合年龄的非侵入性测试，以确定婴儿谁是婴儿猝死综合征（SIDS）的最大风险。对于这个建议，候选人将在杜克大学的斯洛特金博士和哥伦比亚大学的迈尔斯博士的监督下工作。这两位研究人员都是发育神经生物学领域的专家，并在研究密集型机构工作，这些机构将为该计划的成功提供经验。 候选人发展： 1.完成神经生物学和发育神经生物学课程。 2.花大量时间在实验室学习神经生物学技术。 3.测试下面描述的研究目标。 4.发展合作，指导，领导和科学写作的技能。 怀孕期间的尼古丁暴露导致许多神经发育的改变，包括行为障碍，抑郁症，成瘾和SIDS。小岛屿发展中国家是发达国家婴儿死亡的主要原因。吸烟母亲所生的婴儿死于SIDS的可能性高出4倍。来自动物研究的大量证据表明，尼古丁会损害脑干和自主神经系统功能，这与SIDS和其他发育障碍一致。候选人将使用她开发的动物模型，该模型考虑了SIDS死亡的环境，发育和年龄风险因素。该模型的初步数据已经显示，围产期尼古丁暴露会增加死亡率。 具体研究目标： 目的1：验证尼古丁/流感/内毒素模型中初步数据中发现的死亡率 目的2：建立评估自主神经和血压反应的程序 目的3：确定生存率降低的自主/心血管机制。 目的4：通过阻断交感神经或副交感神经通路，检查自主神经反应的具体行动。

DESCRIPTION (provided by applicant): The candidate needs additional knowledge skills in developmental neurobiology to allow her to continue her long-term goals of elucidating factors that affect the health and well-being of infants, and to develop age appropriate, non-invasive tests that will identify infants who are at greatest risk for Sudden infant death syndrome (SIDS). For this proposal the candidate will work under the supervision of Dr. Slotkin, Duke University, and Dr. Myers, Columbia University. Both of these researchers are experts in the field of developmental neurobiology and work at research intensive institutions that will offer the experiences for the success of this plan. Candidate development: 1. Complete course work in neurobiology and developmental neurobiology. 2. Spend extensive time in the laboratory learning neurobiologic techniques. 3. Test the research Aims described below. 4. Develop the skills of collaboration, mentoring, leadership, and scientific writing. Nicotine exposure during pregnancy is responsible for many alterations of neurologic development including; behavioral disorders, depression, addiction, and SIDS. SIDS is the leading cause of infant mortality in developed countries. Infants born to mothers who smoke are 4 times more likely to die of SIDS. Substantial evidence from animal studies shows that nicotine produces impairment of brainstem and autonomic nervous system function consistent with SIDS and other developmental disabilities. The candidate will use an animal model she developed that accounts for environmental, developmental and age risk factors identified for SIDS deaths. Pilot data from this model have already shown an increase in mortality with perinatal nicotine exposure. Specific research aims: Aim 1: Verify the mortality found in pilot data in the nicotine/influenza/endotoxin model Aim 2: Establish procedures for assessing autonomic and blood pressure responses Aim 3: Determine the autonomic/cardiovascular mechanisms underlying the decreased survival. Aim 4: Examine specific actions of autonomic response by blocking sympathetic or parasympathetic pathways with pharmacologic agents.